Vesical Imaging-Reporting and Data System (VI-RADS) Followed by Photodynamic Trans-urethral Resection of Bladder Tumours (PDD-TURBT) to Avoid Secondary Resections (Re-TURBT) in Non-Muscle Invasive Bladder Cancers (NMIBCs)

Summary

Background: In European Association of Urology (EAU) Guidelines, the vast majority of non-muscle-invasive bladder cancers (NMIBCs) undergo a primary transurethral resection of the bladder tumor (TURBT) followed by a repeat TURBT (Re-TURBT). The Re-TURBT is recommended due to the possibility of residual bladder cancer but is unnecessary in many cases by constituting overtreatment. Currently, no diagnostic strategy or predictive tools have been implemented to further stratify who does or does not benefit from Re-TURBT. Recently, an MRI-based Vesical Imaging Reporting and Data System (VI-RADS) score has been developed to stage as to the preoperative probability of muscle invasion, which could potentially exclude those who do not require a Re-TURBT when a primary high-quality resection is delivered. As such, performing TURBT with standard white light (WL) cystoscopy is known to miss many bladder tumours, which may be poorly visible, and a technique known as with photodynamic diagnosis (PDD) results in lower residual tumor and lower early intravesical recurrence rates. PDD is performed using violet light to improve the detection of these lesions not easily visible with WL cystoscopy.

Methods/Aims: The investigators propose an Italian, single-center, phase IV, open-label, non-inferiority, randomized controlled trial, in which participants (n=112) who had already received a mpMRI/VI-RADS score, are randomized to receive PDD-TURBT, no Re-TURBT versus standard of care represented by conventional WL-TURBT followed by WL-Re-TURBT. The primary outcome is proportions of early recurrence in the urinary bladder. Secondary outcomes will include proportions of late BCa recurrence, late disease-free interval, time to progression to MIBC, patient's quality of life assessment, and cost-analysis.

Perspective: The CUT-less trial aims to respond to this unmet need through a non-inferiority randomized clinical study potentially shaping the perspective for a paradigm shift towards a more personalized, socially, and economically sustainable updated NMIBC therapeutic pathway.

Implications: The current clinical trial proposal is aiming to achieve a paradigm shift in the oncological and socio-economical management of urothelial malignancies of the urinary bladder. Our first concern is indeed to guarantee a safe and ground-breaking strategy to manage the pathway of such patients in order to guarantee the non-inferior oncologic safety (and possibly superiority) when compared to the current standard of care.

Additionally, if our hypotheses are confirmed, the investigators will be able to significantly relieve these patients from the oncologic burden of an already invasive and arduous bladder cancer care path. Finally, safely avoiding an unnecessary, expensive surgical procedure will bring significant social and economic benefits to the EU healthcare system and possibly worldwide.

Conditions

• Non-muscle-invasive Bladder Cancer
• Non-Muscle Invasive Bladder Urothelial Carcinoma
• High Risk Non-Muscle Invasive Bladder Urothelial Carcinoma

Interventions

DRUG

PDD-TURBT with hexaminolevulinate (Hexvix®)

In order to undergo PDD-TURBT, all eligible patients in the experimental arm will be administered the photosensitizer hexaminolevulinate (85 mg in 50 ml of phosphate buffered saline, Hexvix®) on an inpatient setting through a urethral catheterization of the participant's bladder. During the PDD-TURBT surgery, the bladder will be illuminated with blue light (wavelength 380-450 nm). The operating rooms of the participant institutions will therefore need to have the specialized equipment consisting in the blue-light source (POWER LED SAPHIRA \[TM\]).

DEVICE

Power Led Saphira (TM)

This is a light source based on LED technology. It can be used for both White Light (WL) and fluorescence applications in blue light (i.e., Photodynamic diagnosis PDD) for visualizing tumor lesions during trans-urethral resection of bladder tumors (PPD- TURBT).

Sponsors & Collaborators

• University of Roma La Sapienza

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-12-22

Primary Completion

2028-12-31

Completion

2031-12-31

Countries

• Italy

Study Locations